Major histocompatibility complex, class II, DQ beta 1, also known as HLA-DQB1, is a human gene and also denotes the genetic locus that contains this gene.[5] The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.
Function
HLA-DQB1 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen-presenting cells (APC: B lymphocytes, dendritic cells, macrophages).[5]
Gene structure and polymorphisms
The beta chain is approximately 26-28 kDa and it contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular protein domains, exon 4 encodes the transmembrane domain, and exon 5 encodes the cytoplasmic tail. Within the DQ molecule, both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation.[5][6]
Disease association
Autism
A four-loci genotype study showed that A*01-B*07-DRB1*0701-
DQB1*0602 (P = 0.001, OR 41.9) and
the A*31-B*51-DRB1*0103-
DQB1*0302 (P = 0.012, OR 4.8) are
positively associated with autism among Saudi patients.
Diabetes
Several alleles of HLA-DQB1 are associated with an increased risk of developing type 1 diabetes.[7][8][9] The locus also has the genetic name IDDM1 as it is the highest genetic risk for type 1 diabetes. Again the DQB1*0201 and DQB1*0302 alleles, particularly the phenotype DQB1*0201/*0302 has a high risk of late onset type 1 diabetes. The risk is partially shared with the HLA-DR locus (DR3 and DR4 serotypes).
Celiac disease
Celiac1 is a genetic name for DQB1, the HLA DQB1*0201, *0202, and *0302 encode genes that mediate the autoimmunecoeliac disease. Homozygotes of DQB1*0201 have a higher risk of developing the celiac disease, relative to any other genetic locus.[10]
Other HLA-DQB1 alleles are associated with a predisposition to narcolepsy,[13] specifically HLA-DQB1*0602, which is carried by over 90% of patients with narcolepsy-cataplexy.[14]
Overview of all the structural information available in the PDB for UniProt: P01920 (HLA class II histocompatibility antigen, DQ beta 1 chain) at the PDBe-KB.
